Background:  Altered metabolism emerged after HAART introduction. In patients treated with protease inhibitors (PI), a high prevalence (30 to 80%) of insulin-resistance and hyperinsulinemia was found, compared with the significantly reduced (< 10%) frequency of altered glucose tolerance and a frank diabetes, although cardiovascular risk is increase by the frequent concomitant dyslipidemia. Patients and methods. The aim of our prospective study is to assess the incidence of hyperglycemia in patients treated with HAART.

Methods:  Both efficacy and safety of either gliclazide or metformin or rosiglitazone were evaluated in patients with altered glucose metabolism, in a randomized, prospective study in which 289 patients who had started a novel PI-based HAART from 1998 to 2002 were prospectively followed for 12 months to detect the frequency of hyperglycemia and its correlates. All enrolled patients had a normal fasting glycemia at start of their novel HAART regimen; 32.5% of these patients were naïve to all ART. Later, all patients with hyperglycemia persisting for ≥ 6 months and resistant to a diet-exercise program of ≥ 3-month duration underwent therapy with gliclazide (80 mg/day), metformin (500 mg twice daily), or rosiglitazone (4 mg/day),and were followed for ≥ 12 months.

Results:  After the 12 prospective months of observation, hyperglycema was reported in 36 of the 289 evaluable patients. During the entire follow-up, glucose abnomalities were usually mild (110 to 140 mg/dL in 28 patients), infrequently moderate (140 to 200 mg/dL in 8 patients), while a hyperglycemia > 200 mg/dL was never seen. Overall, 36 patients exhibited glucose alterations associated with increased C-peptide levels (mean value 7.4 ng/mL), an elevated rate of glycosilated hemoglobin (mean value 9.7), as well as hypertryglyceridemia (mean level 238.1 mg/dL), a patient’s age > 55 years, body mass index > 28, more prolonged duration of overall anti-HIV therapy, and more advanced HIV disease stage. No significant relationship emerged between hyperglycemia and use of specific anti-HIV compounds. A 12-month gliclazide, metformin, or rosiglitazone adjunct achieved a drop of mean serum glycemia of 27.2 mg/dL (p < 0.02), 24.1 mg/dL (p < 0.02), and 30.3 mg/dL (p < 0.02), respectively, vs baseline levels, and without significant differences according to the different administered compounds.

Conclusions:  A PI-based HAART is related to a moderate, but non-negligible tendency toward hyperglycemia and hyperinsulinemia. An oral gliclazide, metformin, or rosiglitazone therapy proved equally safe and effective.

Keywords: Hyperglycemia; Frequency and specific treatment; Randomized therapeutic study